Transmissible spongiform encephalopathies (TSEs) affect a wide range of species including sheep,cattle, mink, humans, deer, elk and others. An issue of particular importance is to determine which TSE diseases can be transmitted to other species especially humans or livestock. To investigate the issue of cross-species transmission we used an animal model involving transmission of hamster scrapie agent to mice (prior to our study mice were considered resistant to hamster scrapie). We found that cross-species transmission between supposedly incompatible hosts can occur but involves a very slow but relentless process requiring several passages in the new host before finally emerging as a recognizable disease. This persistance and eventual adaptation suggests that similar situations could occur in other species combinations. [unreadable] In order to study other aspects of CWD we have developed mice transgenic for deer prion protein. Several lines have been derived that make deer PrPsen and after inoculation with CWD brain homogenates derived from CWD infected deer or elk develop clinical disease and disease-associated PrP-res. These mice are being used to study several aspects of CWD including pathogenesis in infected animals, the influence of differing PrP genotypes and whether persistence occurs in seemingly uninfected animals. They are also being used to develop assays for CWD and to titer infectivity found in naturally infected animal tissues. [unreadable] Several other kinds of transgenic mice have been used over the past few years to investigate a variety of questions regarding the influence of prion protein on interspecies transmission, the role of specific cell types on TSE pathogenesis and kinetics of disease development. It is known that interspecies transmission can involve prion protein interactions between the prion proteins (PrP) of the species involved. We have found that hamster scrapie agent can persist in mice for the mouse's lifespan but not cause clinical disease. (Previously mice were thought to be resistant to hamster scrapie agent).